Effect of structural analogues of propionate and butyrate on colon cancer cell growth

The aim of this study was to evaluate the effects of natural short-chain fatty acids (butyrate, propionate, valerate, acetate) and structural analogues of butyrate and propionate on cell growth and apoptosis in three human colonic adenocarcinoma cell lines (HT-29, Colo-320, and SW-948). We have prev...

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Bibliographic Details
Published in:International journal of colorectal disease 2000-11, Vol.15 (5-6), p.264-270
Main Authors: MILOVIC, V, TELLER, I. C, TURCHANOWA, L, CASPARY, W. F, STEIN, J
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Apoptosis - drug effects
Biological and medical sciences
Bromine - chemistry
Butyrates - chemistry
Butyrates - pharmacology
Cell Division - drug effects
Cell growth
Colonic Neoplasms - drug therapy
Colorectal cancer
Deoxyribonucleic acid
DNA
DNA Damage - drug effects
DNA, Superhelical - metabolism
Dose-Response Relationship, Drug
Fatty acids
Fatty Acids - pharmacology
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Medical sciences
Plasmids - metabolism
Propionates - chemistry
Propionates - pharmacology
Spermine - pharmacology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Time Factors
Tumor Cells, Cultured
Tumors
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Summary:The aim of this study was to evaluate the effects of natural short-chain fatty acids (butyrate, propionate, valerate, acetate) and structural analogues of butyrate and propionate on cell growth and apoptosis in three human colonic adenocarcinoma cell lines (HT-29, Colo-320, and SW-948). We have previously shown that mercapto- and bromo-analogues of butyrate and propionate compete with natural short-chain fatty acids for uptake in the colonocyte. Among naturally occurring short-chain fatty acids, butyrate was the most potent inhibitor of proliferation in all three cell lines. Propionate exhibited a weaker antiproliferative effect, while other short-chain fatty acids (valerate, acetate) were ineffective. Bromo-analogues of butyrate and propionate were more potent proapoptotic agents than butyrate. In contrast to butyrate, the analogues induced strand breaks on isolated supercoiled DNA, the effect being completely reversed by a DNA-protecting agent, spermine. We conclude that bromo-analogues of butyrate and propionate are more potent proapoptotic agents than butyrate in colon cancer cells in culture. Their effect may be a result of direct DNA damage.
ISSN:0179-1958
1432-1262
DOI:10.1007/s003840000257